Bryostatin 1-tamoxifen combinations show synergistic effects on the inhibition of growth of P388 cells in vitro.
This study shows that combinations of bryostatin 1, a novel modulator of protein kinase C currently under clinical evaluation, with the anti-oestrogenic agent tamoxifen caused a large synergistic enhancement of growth inhibition in P388 cells in vitro. The growth-inhibitory effects of bryostatin 1 in the presence of non-inhibitory concentrations of tamoxifen were increased by approximately 200-fold, whereas growth inhibition by tamoxifen in the presence of non-inhibitory concentrations of bryostatin 1 were increased over 30-fold. These data have been confirmed by isobologram analysis. The precise mechanism underlying this effect is unknown, although preliminary data implicating protein kinase C is presented. The magnitude of this synergistic effect, together with evidence of clinical responses seen when these agents were given sequentially in ovarian cancer, merits further study.
McGown
A T
AT
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Jayson
G
G
Pettit
G R
GR
Haran
M S
MS
Ward
T H
TH
Crowther
D
D
D000818:Animals; D054713:Bryostatins; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D007783:Lactones / Q000008:administration & dosage*; D007941:Leukemia P388 / Q000188:drug therapy*; D018942:Macrolides; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D019311:Staurosporine / Q000008:administration & dosage; D013629:Tamoxifen / Q000008:administration & dosage*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage
D054713:Bryostatins; D006131:Growth Inhibitors; D007783:Lactones; D018942:Macrolides; D013629:Tamoxifen; C046785:bryostatin 1; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate